A Histological and Immunohistochemical Study of the Subsynovial Connective Tissue in Idiopathic Carpal Tunnel Syndrome

112

We investigated inflammation in rats performing a low repetition, negligible force (LRNF) or high repetition, negligible force (HRNF) task of reaching and retrieving food pellets at target rates of two or four reaches/min for 2 h/day, for 6-8 weeks. Serum was assayed for 11 cytokines and chemokines; forelimb tissues for four cytokines. Macrophages were counted in forelimb tissues of LRNF rats to add to results from our previous studies of HRNF rats. In HRNF rats, serum IL-1a, IL-1b, TNFa, MIP2, MIP3a, and RANTES were elevated in weeks 6 and 8. In contrast, only MIP2 and MIP3a increased in serum of LRNF rats. In 8 week HRNF reach limb tissues, IL-1a, IL-1b, TNFa, and IL-10 increased in distal bones, IL-1a and -b in muscles, and TNFa in tendons. Only IL-10 increased in LRNF reach limb muscles in week 8. Serum IL-1a and MIP2 correlated with macrophages in LRNF loose connective tissues, serum MIP3a and MIP2 correlated negatively with grip strength, while serum TNFa, MIP3a, and MIP2 correlated positively with total number of reaches. Thus, several tissue and circulating cytokines/chemokines increase in an exposure dependent manner following short-term performance of repetitive reaching tasks and correlate with macrophage infiltration and decreasing grip strength. Keywords: cytokines; chemokines; macrophages; repetitive motion injury; WMSD Repetitive motion injuries (RMI) of the wrist and hand are painful, potentially disabling, and costly. Recent work suggests that RMIs induce injury in several tissue types in animal models, 1-6 as well as an early inflammatory response at the tissue level. 2,3,[7][8][9] Increases in four circulating inflammatory mediators, C-reactive protein, interleukin 1 beta (IL-1b), IL-6, and tumor necrosis factor alpha (TNFa) have also been shown to increase in patients with upper extremity overuse disorders. 10 The factors triggering underlying pathophysiological responses are still under investigation, which impedes progress toward their primary and secondary prevention.Using a rat model, we have reported that repetitive reaching causes injury and wide-spread increases in macrophage influx into musculotendinous tissues and peripheral nerves, extraneural fibrosis, decreased nerve conduction, and decreased grip strength. [2][3][4]7,9 The macrophage response is associated with increased inflammatory cytokines in the median nerve, 9 and increased serum IL-1a following HRNF task performance. 2 A variety of inflammatory mediators including cytokines and chemokines are released by injured cells and infiltrating macrophages. 9,11 Although serum cytokine and chemokine response patterns to exercise of varying intensities 12-15 and multiple organ trauma and fractures have been studied, [16][17][18] exposure to more chronic, lower levels of injury are not yet well characterized.Here, we examine several cytokines and chemokines in forelimb musculoskeletal tissues and serum to identify their response profiles, as well as potential cellular sources, after the performance of a voluntary repetitive ...

Section: Discussionmentioning

confidence: 99%

Serum and tissue cytokines and chemokines increase with repetitive upper extremity tasks

Barbe

Elliott

Abdelmagid

et al. 2008

112

“…19 Causes of tenosynovial swelling include overgrowth of the type 1 and 3 collagens that constitute the tenosynovium. 4,20 Chikenji et al 7 reported that repetitive mechanical stimulation of the tenosynovium induced the expression of transforming growth factor-b1, which in turn induced the expression of type 3 collagens.…”

Section: Discussionmentioning

confidence: 99%

“…Tenosynovial tissues were flash frozen and stored at À80˚C until mRNA isolation and immunohistochemical examination were performed as described below. We extracted mRNA and used quantitative real-time polymerase chain reaction (PCR) to compare the expression levels of genes encoding Wnt1,2,3,4, 5a, 5b,6, 7a, 7b, 8a, 8b, 9a, 9b, 10a, 10b,11,and 16 between the groups. Expression of genes encoding cell proliferation factors, such as estrogen-responsive finger protein (Efp), epidermal growth factor receptor (EGFR), heparin binding-epidermal growth factor-like growth factor (HB-EGF), insulin-like growth factor-1…”

mentioning

confidence: 99%

“…Furthermore, median nerve compression and restricted range of motion consequent to these characteristics may be among the causative factors associated with ICTS. 3,4 In addition, few inflammatory changes have been observed in the flexor tenosynovium in ICTS 5 ; instead, blood vessel wall destruction and angiogenesis accompanied by a degree of edema may be detected. 3 Increased expression of cell proliferation factors, such as vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF), in synovial cells is a feature of ICTS.…”

mentioning

confidence: 99%

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Enhanced expression of Wnt9a in the flexor tenosynovium in idiopathic carpal tunnel syndrome

Yamanaka

Menuki

Zenke

et al. 2015

This study aimed to clarify the association between abnormal Wnt signaling and the cause of idiopathic carpal tunnel syndrome (ICTS) and whether an association exists between Wnt signaling and cell proliferation in the flexor tenosynovium. The subjects included nine patients with ICTS; the controls were nine patients with distal radius fractures without any symptoms of carpal tunnel syndrome. We extracted mRNA from the flexor tenosynovium and compared the expression levels of genes encoding 17 types of Wnt in both subjects and controls via quantitative real-time polymerase chain reaction (PCR). Expression levels of factors involved in cell proliferation, such as estrogen-responsive finger protein, epidermal growth factor receptor, heparin binding-epidermal growth factor-like growth factor, insulin-like growth factor-1, and vascular endothelial growth factor (VEGF) were also measured using quantitative real-time PCR. In addition, we compared the Wnt and MIB-1 protein expression levels to clarify the effect of Wnt on cell proliferation. Quantitative real-time PCR revealed significantly greater expression of the gene encoding Wnt9a in subjects with ICTS than in controls and also revealed a positive correlation between the expression of genes encoding Wnt9a and VEGF in subjects with ICTS. Quantitative evaluation using immunohistochemical staining also indicated more marked Wnt9a expression in subjects than in controls. However, there was no relationship between the expression of Wnt9a and the cell proliferation index MIB-1. These results indicate that Wnt9a expression is enhanced in ICTS and that Wnt9a may be involved in VEGF expression in ICTS. Keywords: idiopathic carpal tunnel syndrome; Wnt signal; vascular endothelial growth factor; MIB-1; flexor tensynovium Carpal tunnel syndrome (CTS) has the highest incidence among all entrapment syndromes, with an overall prevalence of approximately 3.8%. 1 The majority of CTS cases are idiopathic. 2 Although the exact pathological mechanism of idiopathic CTS (ICTS) remains unknown, some characteristic features of ICTS have been revealed. For example, ICTS is associated with fibroblast proliferation and collagen fiber overgrowth. Furthermore, median nerve compression and restricted range of motion consequent to these characteristics may be among the causative factors associated with ICTS. 3,4 In addition, few inflammatory changes have been observed in the flexor tenosynovium in ICTS 5 ; instead, blood vessel wall destruction and angiogenesis accompanied by a degree of edema may be detected. 3 Increased expression of cell proliferation factors, such as vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF), in synovial cells is a feature of ICTS. 6,7 However, the mechanism by which the expression of these factors increases remains unknown.Wnt signaling controls initial cell development, morphogenesis, and organogenesis as well as postnatal cell proliferation, differentiation, and activity, and 19 types of Wnt ligands have been identifie...

“…The median nerve always gets mechanical stress with movement of the wrist, and the dynamic limit is dependent on the positional relationship between the median nerve and the surrounding tissues. When the elevation in carpal tunnel pressure is caused by an increased volume of fluid and/or synovial membrane within the canal, 18 movement of the nerve along with movement of the wrist becomes limited, and consequently compression and traction on the nerve cause neuropathic pain. 19 Chronic compression is the result of repeated episodes of mild acute compression.…”

Section: Discussionmentioning

confidence: 99%

Intraneural blood flow analysis during an intraoperative Phalen's test in carpal tunnel syndrome

Yayama

Kobayashi

Awara

et al. 2010

Phalen's test has been one of the most significant of clinical signs when making a clinical diagnosis of idiopathic carpal tunnel syndrome (CTS). However, it is unknown whether intraneural blood flow changes during Phalen's test in patients with CTS. In this study, an intraoperative Phalen's test was conducted in patients with CTS to observe the changes in intraneural blood flow using a laser Doppler flow meter. During Phalen's test, intraneural blood flow showed a sharp decrease, which lasted for 1 min. Intraneural blood flow decreased by 56.7%-100% (average, 78.0%) in the median nerve relative to the blood flow before the test. At 1 min after completing the test, intraneural blood flow returned to the baseline value. After carpal tunnel release, there was no marked decrease in intraneural blood flow. This study demonstrated that the blood flow in the median nerve is reduced when Phalen's test is performed in vivo. ß